The objective of this series of studies is to determine the effect of antigenic stimulation on the progression of SIV pathogenesis and viral load in the SIV/rhesus macaque model system. In one experiment, intramuscular immunization of SIV infected rhesus macaques with low-dose bacterial superantigens resulted in a 5-50 fold increase in plasma viral RNA levels as determined by QC-PCR in the two weeks post-immunization compared to unimmunized, SIV infected controls. In a second experiment, SIV infection following a series of immunizations with DPT vaccine resulted in rapid disease progression in five of six treated rhesus macaques, despite development of a humoral immune response against SIV. The high frequency of rapid disease progression in pre-immunized animals differed significantly from frequency (10/31) observed among unimmunized and similarly siv infected, historical controls (p=0.030; Fisher's exact test). The results of both experiments support the hypothesis that antigenic stimulation increases viral replication and accelerates SIV disease progression. Analysis of QC-PCR data suggests that it is the initial rate of viral clearance, rather than the peak level or final plateau level of virus load, that correlates with (or predicts) disease course. Additional experiments are in progress to confirm and refine these observations.